SUN-304 Associations of BMI Changes and Adipokines with Survival and Treatment Response During Myeloma Induction Therapy

Abstract Disclosure: R. Thirugnanasambandam: None. R. Firestoe: None. A. Derkach: None. T. Shekarkhand: None. C. Rueda: None. K. Maclachlan: None. M.L. Hultcrantz: None. S. Mailankody: None. D. Patel: None. H. Landau: None. G. Shah: None. M. Scordo: None. H. Hassoun: None. A.M. Lesokhin: None. S. Giralt: None. M. Pollak: None. N. Korde: None. S.Z. Usmani: None. C.R. Tan: None. U.A. Shah: None. Background:Elevated BMI is a known risk factor in newly diagnosed multiple myeloma (NDMM), with extremes (underweight and obesity) linked to poor survival. While metabolic disorders are characterized by BMI fluctuations and adipokine imbalances, their impact during induction therapy remains unclear. We aimed to explore the relationship between BMI changes, adiponectin-leptin (AL) ratio, and survival outcomes in NDMM.Methods:We retrospectively analyzed 389 NDMM patients (pts) treated with either Carfilzomib, Revlimid & dexamethasone (N=191) or Velcade, Revlimid & dexamethasone (N=198) from 01/2016 - 12/2022. Data on BMI, age, gender, Revised International Staging System (RISS), cytogenetics, cardiac history, diabetes history were collected. Pts were classified by BMI into underweight (BMI < 18.5), normal (BMI 18.5-24.9), and overweight/obese (BMI ≥25). BMI changes during induction therapy were categorized as weight stable (BMI change <5%), weight loss (BMI decrease ≥5%), and weight gain (BMI increase ≥5%).We also measured markers of metabolic health (adiponectin, leptin, and adiponectin/leptin (AL) ratio) using biobank specimens from 128/389 pts at baseline, 57 of whom had paired post-induction samples. Associations between baseline BMI, BMI change, and AL ratio with progression-free survival (PFS) and overall survival (OS) were assessed using multivariable Cox regression and landmark analysis. Results:At baseline, 1% of pts were underweight, 22% had normal BMI, 73% were overweight/obese, and 4% had missing data. During induction, 65% were weight stable, 19% experienced weight gain, and 16% experienced weight loss. Older pts were more likely to lose weight during induction (-0.03kg/m2 per year increase in age, p=0.0005), and pts with RISS 2-3 were more likely to experience weight changes compared to RISS 1 pts (weight loss: 20% vs 10%; weight gain: 20% vs 15%; p=0.0075).Compared to weight loss, weight gain during induction was linked to higher progression risk (HR 2.12, p=0.028), while weight stability did not significantly impact PFS. Elevated BMI (as a continuous variable) correlated with worse OS at baseline (HR 1.05, p=0.02) and post-induction (HR 1.05, p=0.03). Consistent with prior evidence, RISS3, and high-risk cytogenetics predicted worse outcomes.A high baseline BMI was associated with a high blood leptin (p<0.001), low adiponectin (p=0.0002), and a low AL ratio (p<0.0001), an association which persisted for post-induction BMI. Higher AL ratio following induction was associated with improved OS (HR=0.02, p=0.04).Conclusion: Weight gain during induction was associated with worse outcomes, while a higher post-induction AL ratio correlated with improved survival. These findings underscore the prognostic value of adipokine dynamics and highlight the need for targeted metabolic interventions to address adipocyte dysfunction in myeloma treatment. Presentation: Sunday, July 13, 2025